Abstract

Objective

To evaluate the cost-effectiveness of treating sepsis with HA-1A monoclonal antibody.

Design

Cost-effectiveness analysis based on a randomized, double-blind, placebo-controlled
trial.

Setting

Hospitalized patients with sepsis.

Patients

Effectiveness data were based on the results of a trial with 543 patients (mean age,
58 years) with sepsis and suspected gram-negative infection that was subsequently
confirmed in 36%.

Intervention

Effectiveness data were developed using the statistically significant difference in
in-hospital mortality among patients with gram-negative sepsis, comparing those treated
with HA-1A with those on placebo.

Main outcome measures

The incremental cost of care and years of life saved for patients with sepsis were
calculated using data from the trial and using modeling techniques when clinical or
economic variables were unknown. 2 different management strategies were assessed:
"treat" all patients with sepsis or "test" and then treat only patients with positive
test results. The "test" strategy was hypothetical and would depend on development
of a rapid test for gram-negative sepsis. Sensitivity analyses were used to test several
assumptions.

Main results

The incremental lifetime cost of the "treat" strategy was $5650 per patient. The average
benefit to treated patients was 5.4 deaths averted per 100 treated patients. The cost-effectiveness
of therapy using the "treat" strategy was

$24 100 per year of life saved. On a population basis, the annual cost of HA-1A therapy
in the United States using this strategy would be $2.3 billion. Using the "test" strategy
(which would reduce the number of false positives being treated), the cost-effectiveness
of therapy was $14 900 per year of life saved. The corresponding annual cost for the
United States population would be $1.3 billion. In the sensitivity analyses (varying
the proportion of patients with gram-negative bacteremia, the life expectancy of survivors,
and drug and hospitalization costs), the ratios for the treat strategy ranged from
$8400 to $110 200 per year of life gained.

Conclusion

The cost-effectiveness ratio for treating all patients with suspected gram-negative
bacteremia was $24 100 per year of life saved.

Commentary

This paper highlights 2 critical issues faced by hospitals and physicians as they
contemplate the potential release of HA-1A, the monoclonal antibody against bacterial
endotoxin that is projected to be life-saving as well as expensive. First, because
the expected benefit from treatment is years of life gained, concentrating its use
in patients with longer postsepsis life expectancies will be most cost-effective.
At least 1 institution has considered including prognosis in their decision criteria
for HA-1A (1). Second, available evidence suggests that HA-1A is only useful in treating sepsis
due to gram-negative bacteremia. Hence, a critical determinant of the cost-effectiveness
of HA-1A is the proportion of treated patients who have gram-negative infection. This
article shows that treating populations with lower proportions of gram-negative bacteremic
patients will substantially increase costs; for example, if 10% of the treated population
has gram-negative infection, the cost rises to $65900 per year of life saved. This
sensitivity to patient selection is stimulating pharmacy and therapeutic committees
around the country to create policies that will restrict HA-1A use to well-defined
patient groups. This sensitivity also led Schulman and colleagues to model the effect
of a hypothetical rapid diagnostic test for gram-negative bacteremia. Including the
cost of the test, the authors estimate that costs per year of life saved would decrease
38% and save $1 billion annually.

This lucid economic analysis shows how combining available data with sensitivity analysis
can lead to important insights. Nevertheless, these insights, like most of the discussions
of HA-1A, derive from a single clinical trial, and further trials are needed to confirm
the drug's effectiveness.